The central hypothesis of this continuing research program is that readily accessible body fluids and/or physiological functions provide biomarkers which may be predictive of: a) exposure, b) adverse effects, and/or c) unusual susceptibility, to toxic substances in the environment. This Program Project includes 12 integrated projects focused around this central theme: Project 1 will continue investigations on glutathione and glutathione biosynthesis as an integrative biomarker for oxidative damage induced by a variety of chemicals found at hazardous waste sites. Project 2 is now applying urinary porphyrin concentration as biomarkers of trace metal, especially mercury, to human populations. Project 4 is continuing studies with freshly isolated human blood lymphocytes to determine if the "fingerprint" of P450 gene products can be used as a biomarker of exposure, and in collaborate with other projects in applying a CYP2D6 polymorphism molecular assay to human populations exposed to toxic chemicals as a potential biomarker of susceptibility. Project 5 will renew investigations on the development of natural and genetically engineered populations of higher plant species to effectively degrade trichloroethylene and other chemicals commonly found at hazardous waste sites. Project 6 will continue work on the development of biological treatment systems for removing chlorinated organic contaminants in groundwater, using mixed microbial cultures in a biological reactor. Project 7 will examine wildlife as biomarkers of exposure to toxic chemicals at hazardous waste sites, using starlings and deer mice inhabiting such sites, and applying biomarkers developed by other projects. Project 8 will continue to examine the presence of oxidative DNA damage as a biomarker of adverse ecological impact in fish exposed to highly contaminated sediments at a Superfund site in Puget Sound. Project 10 will continue to evaluate physiologically-based pharmacokinetic modeling of inter-individual differences in absorption, metabolism and excretion of alkylbenzenes in humans following controlled inhalation exposures. Project 11 will continue a case-control ecogenetic epidemiology study to evaluate if oxidative stress from environmental pollutants, particularly metals and pesticides, is a significant risk factor for Parkinson's disease, and will utilize biomarkers developed in other projects to determine potential genetic susceptibility as a modifier of risk. project 12 is a follow-up epidemiology study of workers occupationally exposed to styrene, and will examine for the first time the prospective relationship between chronic exposure to PCE and symptoms, neurobehavior, neurophysiologic and neurochemical biomarkers of CNS dysfunction. Administrative, BioAnalytical and Training Cores are proposed to foster the productivity and integration of these studies.